Radiopharmaceuticals are radioactive drugs which can have either diagnostic or therapeutic applications. In diagnostic nuclear medicine, the radionuclide is used as a tracer to provide functional information about the tissue under investigation [1-2]. In contrast, therapeutic radionuclides should have particulate radiations with an in vivo range sufficient to destroy the target tissue but not so long as to cause collateral damage. The nuclear requirements for either diagnosis or therapy are seldom met by the radionuclides of the biologically ubiquitous elements such as C, H, N, O, etc., but oblige the use of biologically unimportant elements, almost all of which are metallic. For example, several non-conventional metallic radionuclides, such as 64Cu, 86Y, and 89Zr, have been applied to positron emission tomography (PET) probes [3]. These metallic PET isotopes are usually characterized by longer half-lives, allowing the evaluation of radiopharmaceutical kinetics in same subject to be achieved by successful PET imaging over several hours or even days. Among these metallic radionuclides, 64Cu (t1/2=12.7 h; β+ 655 keV, 17.8%) has attracted considerable interest because of its favorable decay half-life, low β+ energy, and commercial availability [4].
Click chemistry offers chemists a platform for general, modular and high yielding synthetic transformations for constructing highly diverse molecules [5]. The Huisgen 1,3-dipolar cycloaddition reaction, which fuses an azide and an alkyne together, and provides access to a variety of five-membered heterocycles, has become of great use in labeling studies, the development of new therapeutics and nanoparticles, and in protein modification [6]. However, the Huisgen 1,3-dipolar cycloaddition reaction often requires the presence of catalytic amounts of non-radiolabeled Cu(I) ions, which interfere with radiometals and make click reaction impossible for the direct construction of radiometal-labeled probes.
To the best of our knowledge, the catalyst-free click reaction has not yet been employed in the radiometal-labeled probes.